The gender of the individual coming into being is already fixed on a chromosomal level during the fertilization of the ovum. Gender differentiation occurs during embryogenesis. Disturbances in sexual differentiation can arise due to chromosome anomalies, gene mutations and exogenous or endogenous influences, which are often observed during puberty and cause patients to consult a doctor.

00:02
Let’s do Congenital Adrenal Hyperplasia.
00:04
Another cause of adrenal insufficiency, but
let’s get away from the adrenals being damaged,let’s get away from the pituitary being
damaged.
00:15
Congenital adrenal hyperplasia, as the name
implies, how old is your patient?A child.
00:20
What’s going on in the child?Enzyme deficiency.
00:26
Here, in the very beginning section of adrenal
patho-physiology, I walked you through, ingreat detail, the physiology of your adrenal
cortex with your various enzymes.
00:37
Name me the enzyme that will take you from
zona glomerulosa into the zona fasciculate.
00:42
17 alpha-hydroxylase.
00:45
Name me the enzyme that will take you from
the first step of your zona glomerulosa, fasciculata,reticularis from your pregnenolone into progesterone.
00:56
3 beta- hydroxysteroid dehydrogenase.
00:58
We talked about that.
01:00
Give me the next two enzymes that we will
be focusing upon.
01:03
21 and 11, go in chronological order.
01:08
Of all the enzymes that you want to know,
which one do you want to know for sure?90 percent of your congenital adrenal hyperplasia…90 percent of congenital adrenal hyperplasia
is due to 21 beta-hydroxylase insufficiency,that’s where you look first.
01:28
Be smart about how you study.
01:31
What about the other enzyme deficiencies,
could they occur?Yes, of course.
01:35
The other five percent is actually 11 beta,
that’s already 95 percent of all congenitaladrenal hyperplasia.
01:42
You have a measly three percent for the other
enzymes.
01:45
Whatever, I’m not even going to discuss
them.
01:47
So, I’ll do the 95 percent obviously.
01:51
What happens?Child and when this occurs, enzyme is not
present.
02:00
If the enzyme isn’t present, it doesn’t
matter which one actually and if there isn’t,then you don’t have enough cortisol.
02:07
If you don’t have enough cortisol, what’s
the feedback?ACTH.
02:14
All congenital adrenal hyperplasia will have
patients… will not have sufficient cortisolas a child; all congenital adrenal hyperplasia
patients as a child will have increased ACTH.
02:29
All congenital adrenal hyperplasia will have
hyperplasia of the adrenal, why?ACTH is bombarding both of the adrenals granted
you don’t have the enzymes, but what willbe the adrenals undergoing?Hyperplasia.
02:47
Is that clear?That’s why your child doesn’t have cortisol,
that’s why your child has excess ACTH.
02:55
The next question I always get from residents
and students, “Dr. Raj, why did these childrennot have hyperpigmentation around the oral
mucosa?”That is an excellent question.
03:05
Because you don’t have enough influence
of your pre… proopiomelanocortin like youwould with Addison’s.
03:10
Interesting, isn’t it?Darn good question, but you will not find…
that’s not what your focus is, the hyperpigmentation,no, no, no.
03:20
Infants, children.
03:21
Take a look at this.
03:23
Here you have… that is not a penis, that’s
a clitoris that’s undergoing enlargement.
03:29
This is a female?Yes.
03:31
So, that’s a vagina?That is correct.
03:35
What is going on?It’s called virilisation.
03:37
What’s the most important sign of virilisation?What does virilisation mean?It means actual, physical attributes of a
male in a female; increased muscle mass ina female, increased acne in a female.
03:52
But, the most important sign will be clitoromegaly.
03:57
There are two major enzyme deficiencies.
03:59
We’ve seen this picture before, I’m not
going to walk you through this again.
04:02
Your focus will be on 21 beta hydroxylase
deficiency and when there is 21 beta hydroxylasedeficiency, you’re not going to form any
mineralocorticoid, the blood pressure’sdecreased and if that first column is your
glomerulosa, you cannot form any mineralocorticoid.
04:19
What’s that blue box forming?Good, cortisol.
04:23
There’s no cortisol, there’s increased
ACTH.
04:27
Now, you can see the feedback, what happens
to both the adrenals?Hyperplasia, but you can’t go through your
fasciculate.
04:37
You are then forced into the deepest layer
of the cortex which is the green box, thatis your reticularis.
04:46
What are you producing there?Androgen, aha, excessively.
04:52
In a young this… remember this started in
utero, so of course, the clitoris looks likea penis, clitoromegaly.
05:04
And when it comes down to your cortisol, your
blue layer, I’ll run through that quicklybecause we’ve already done all these.
05:13
We’ve done this earlier when I began the
discussion of adrenocortical patho-physiology.
05:20
If you’ve missed that discussion, please
go back and take a look at our extensive discussionof adrenocortical patho-physiology while I
walk you through layer by layer by layer andits functioning and what you’re producing.
05:35
Your focus here in this pathology will be
21 beta-hydroxylase.
05:40
The middle bar that you see there 21 beta,
that enzyme will be deficient.
05:45
If you take a look at the glomerulosa, you
do not form any mineralocorticoid, that childis going to have decreased blood pressure.
05:52
You’re not going to have… that child is
not going to have any cortisol, you’re goingto shunt into the reticularis the green box
excessively, having increased androgen.
06:03
Here’s a table to summarize all of your
congenital adrenal hyperplasia.
06:07
Let’s first begin with 21 beta, 90 percent
of your cases, this is your priority.
06:11
Remember that virilisation, I showed you clitoromegaly.
06:14
There will be salt-wasting, your patient will
have hypotension.
06:18
There isn’t enough aldosterone, there will
be hyponatremia, hyperkalemia.
06:22
The problem is this, enzyme deficiency you
can’t form cortisol, but you sure as heckwill have 17- hydroxyprogesterone elevated,
elevated, elevated.
06:33
You’re going to shunt into your reticularis
therefore, you will have increased androstenedioneand androgen.
06:38
What’s your treatment here?It is going to be glucocorticoid for sure
and also mineralocorticoid because in 21 beta…go back and take a look at the picture, you’re
not forming any.
06:49
Now, we have 11 beta, this is five percent;
these are the only two that I’ll cover,the rest are a measly three percent.
06:58
The rest including 17-hydroxy or 17 alpha-hydroxylase
and the other one being 3 beta-hydroxysteroiddehydrogenase.
07:05
If it’s 11 beta, I’d like for you to pay
attention here though.
07:10
If it’s 11 beta, what ends up happening
here is that you will have too much 11 deox.
07:16
Physiologically, 11-deox has what kind of
mineralocorticoid activity?Very weak, but pathologically, you find it
to be excessive.
07:27
Take a look at the diagnostic study where
we see high 11-dexoycorticosterone… welcometo 11 deox that then causes… you see where
I have put in bold hypertension?So, imagine connecting the dots, high 11-deox
causes hypertension, as simple as that.
07:49
So, you have excessive mineralocorticoid activity.
07:52
So, why in the world would you want to give
mineralocorticoid as being part of management?That makes no sense.
07:58
Therefore, glucocorticoid therapy only.
08:01
Do you see how everything’s connected?Obviously, here, you’re going to shunt into
reticularis.
08:05
Here, once again, virilisation, welcome to
clitoromegaly.
08:09
Just to be complete, here’s your 17 alpha-hydroxylase,
go back and take a look at the picture, youare stuck in your glomerulosa.
08:17
You’re not going to have virilisation because
you cannot go into the reticularis, it israre.
08:24
You’re not going to have virilisation in
this patient.
08:26
And by the way, just to make sure we’re-we’re
clear, so obviously, if it’s a female andit’s a child, that will be clitoromegaly,
but how... what do you call excessive masculinizationin a boy?It’s just called precocious puberty.
08:39
What does that mean?It’s just puberty comes way early in that
boy because of increased masculinization.
08:45
Then you have 3 beta-hydroxysteroid dehydrogenase.
08:48
Once again, very, very rare; something called
male pseudo-hermaphroditism, keep that inmind for 3 beta-hydroxysteroid.
08:57
Once again, these two enzyme deficiencies
only make up three percent.

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